HIV RESISTENCE/ HIV TROPISM AREV I R 2 0 1 8 S TA D T H OT E L A - - PowerPoint PPT Presentation

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HIV RESISTENCE/ HIV TROPISM AREV I R 2 0 1 8 S TA D T H OT E L A - - PowerPoint PPT Presentation

Sep 24, 2022 716 likes •1.17k views

HIV RESISTENCE/ HIV TROPISM AREV I R 2 0 1 8 S TA D T H OT E L A M R M E RT U R M , K L N 0 4 . 0 5 . M A I 2 0 1 8 Dr. Stefan Scholten In den RingColonnaden F I NANCI AL DI SCL OSURE Abbott/abbvie, BMS, Gilead, GSK,

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HIV RESISTENCE/ HIV TROPISM

AREV I R 2 0 1 8

S TA D T H OT E L A M RÖ M E RT U R M , K Ö L N 0 4 . – 0 5 . M A I 2 0 1 8 In den RingColonnaden

  • Dr. Stefan Scholten
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F I NANCI AL DI SCL OSURE

Abbott/abbvie, BMS, Gilead, GSK, Hexal, Hormonsan, Janssen-Cilag, MSD, TAD, ViiV Healthcare

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Three cases:

  • One of those patients … (an update and new development)
  • It‘s never as easy as one thinks!
  • Always ask twice!
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Three cases:

  • One of those patients …(an update and new development)
  • It‘s never as easy as one thinks!
  • Always ask twice!
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SLIDE 5

44 years, male, MSM Ethnicity: caucasian (spanish) Date of HIV infection: unknown Date of HIV Diagnosis: 1991 CDC-Classification: C 3

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Pneumocystis jiruvecii Pneumonia Candida-oesophagitis CMV – infection caMRSA „USA 300“ Prior medical conditions:

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ART UNTIL 2007 – THE VL WAS NEVER FULLY SUPPRESSED!

Diarrhea !!! Nausea and abdominal pain ISR under the use of T-20 Lipodystrophy Pillburden „Drug-Holidays“

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SLIDE 8

GT resistance test 07/2007 Tropism (Trophile): Dual/Mixed INI: Y143R FI: n.d. NRTI: M41L E44D D67N T69D V75M V118I M184V L210W T215Y NNRTI: K101E G190S PI: L10I V32I L33F M46I I47V F53L I54M Q58E N83D L90M

ART commenced 01.08.2012 in DTG CUP:

KVX + LPV/r + SQV + ETR + MRV + DTG (2x50mg) Since then he contracted his first syphillis, 3 months later an acute Hepatitis C (GT1a) Then it became clear that he was frequently slamming Crystal Meth He developed a major depression and borderline personality disorder (ongoing)

ART in ETR EAP: KVX + LPV/r + SQV + ETR + T20

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1 10 100 1.000 10.000 100.000 1.000.000

Dez 10 Jun 11 Dez 11 Apr 12 Aug 12 Sep 12 Okt 12 Nov 12 Feb 13 Mai 13 Nov 13 Mai 14 Nov 14 04.02.2015 19.02.2015 03.03.2015 Apr 15

HIV RNA [Kopien/ml] 1 10 100 1.000 10.000 100.000 1.000.000 10.000.000 100.000.000 HCV RNA [IU/ml]

< 40

3TC

1-0-0

3TC ABC

  • “-

ABC ETR

1-0-1

ETR LPV

2-0-2

LPV SQV

2-0-2

SQV T20 T20 MVC

1-0-1

MVC DTG

1-0-1

DTG

< 40 n.d. < 12

LDV/SOF

HCV-RNA und HCV Therapie

39602

Fibroscan 2013: 8,4 kPa Fibroscan 19.01.2015: 14,4 kPa

SVR

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SLIDE 10

2018

LTFU since 03/17 - Last ART prescription 03/17 Showed up again on 23.02.18 Reports having taken at least ONE (blistered) DOSE

(morning or evening)

  • nce in a while – estimated every third day

HIV RNA (23.02.) <40 cps/ml (!)

ART simplification appears to be a paramount necessity - options?

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SLIDE 11

+V38A L45M

RESISTANCE TESTS 2007 / 2012 PRESENT ART: 3TC/ABC+ETR+LPV/R+SQV+DTG+MVC

+L100I +L100I +L100I +L100I

2012 2007 2012 2007 2012 2007

≠F53L ≠F53L ≠F53L ≠F53L ≠F53L ≠F53L ≠F53L

2012 2007

+L74M, T97A, Y134R +L74M, T97A +L74M, T97A

INI naiv FI - naiv 2012 2007 NRTI NNRTI FI PI INI CCR5

FPR 7,4% (fraglich R5-trop)

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Patient reports of increasing inability to adhere, asks if „less“ is possible? … is Fostemsavir (ViiV attachement inhibitor expected in 2018) an option? Could this ART be an Option: DTG bd + MRV bd + Fostemsavir (dose?) ? … what is to do, if he is not coping until 2018

(AGAIN a single named patient use)????

HCV-PCR remains negative and HIV PCR remains <40 cps/ml

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Option 1: Leave everything as it is … (he is taking only half his ART every third day !!!!) Option 2: D/C/F/TAF + DTG/RPV + MRV 300 qd ????? Option 3: DTG + MK1439(Doravirine)+ MRV +/- Ibalizumab (Trogarzo) iv. every 2 weeks ???

(Trogarzo = 118.000,- $ / year)

Option 4: X + fosTemsavir ??? (is to be given TWICE DAILY!!!) ??? Option 5: X + TPV/r ?????????????? (twice daily, diarrhea, pillburden, side effects)

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WHAT are our options now ???

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SLIDE 14
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? ?

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Three cases:

  • One of those patients …(an update and new developement)
  • It‘s never as as easy as one thinks!
  • Allways ask twice !
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MSM, German, 62 years of age, Retired federal law enforcement officer, diplomatic corps HIV diagnosis 1996 CDC stage C3 First ART 1997

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DIAGNOSES

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ART HISTORY

First ART: 03/97 d4T, ddI, NFV 09/2001 University Hospital Bonn HIV PCR: >100.000 cps/ml CD4: <200µl Diag: Cryptosporidiosis, Syphilis Resistance test: multiple NUC and PI Mutations New ART 10/2001: ABC, 3TC, TDF, EFV, LPV/r Soon after that -> LTFU due to transfer abroad Reappeared in my practice in Cologne 2010

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RESISTANCE TEST 2010

Tropismus: X4-trop (1,7% FPR) Truvada Intelence Prezista/r (b.i.d.) Isentress

HIV VL 7868/ml; CD4: 186/µl (14,3%)

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1 10 100 1.000 10.000 100.000 1.000.000 10.000.000

A u g 1 O k t 1 D e z 1 F e b 1 1 M a i 1 1 J u l 1 1 S e p 1 1 D e z 1 1 F e b 1 2 M r z 1 2 J u n 1 2 S e p 1 2 N

  • v

1 2 D e z 1 2 F e b 1 3 M a i 1 3 A u g 1 3 N

  • v

1 3 F e b 1 4 J u l 1 4 O k t 1 4 F e b 1 5 J u l 1 5 N

  • v

1 5 J u l 1 6 A u g 1 6

HIV RNA [Kopien/ml] 200 400 600 800 1.000 1.200 1.400 1.600 1.800 2.000 CD4 [Zellen/µl]

67 9,8% <40 (n.d.) 64

HIV RNA HCV RNA CD4 TDF FTC ETR DRV/r (bid) RAL

acute HCV GT 4 moderately raised transaminases Albumin normal Thrombocytes normal

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SLIDE 22

1 10 100 1.000 10.000 100.000 1.000.000 10.000.000

A u g 1 O k t 1 D e z 1 F e b 1 1 M a i 1 1 J u l 1 1 S e p 1 1 D e z 1 1 F e b 1 2 M r z 1 2 J u n 1 2 S e p 1 2 N

  • v

1 2 D e z 1 2 F e b 1 3 M a i 1 3 A u g 1 3 N

  • v

1 3 F e b 1 4 J u l 1 4 O k t 1 4 F e b 1 5 J u l 1 5 N

  • v

1 5 J u l 1 6 A u g 1 6

HIV RNA [Kopien/ml] 200 400 600 800 1.000 1.200 1.400 1.600 1.800 2.000 CD4 [Zellen/µl]

67 9,8% <40 (n.d.)

Therapieverlauf 44088

64

HIV RNA HCV RNA CD4 TDF FTC ETR DRV/r (bid) RAL 12 weeks IFN+RBV stop due to non response & major depression

21,8%

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SLIDE 23

RESISTANCE TEST 2015

(PROVIRAL DNA) 11/2015

Tropismus (08/10): X4-trop (1,7% FPR)

FTC

= ART Auswahl

DTG TDF ETR DRV RAL

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1 10 100 1.000 10.000 100.000 1.000.000 10.000.000

A u g 1 O k t 1 D e z 1 F e b 1 1 M a i 1 1 J u l 1 1 S e p 1 1 D e z 1 1 F e b 1 2 M r z 1 2 J u n 1 2 S e p 1 2 N

  • v

1 2 D e z 1 2 F e b 1 3 M a i 1 3 A u g 1 3 N

  • v

1 3 F e b 1 4 J u l 1 4 O k t 1 4 F e b 1 5 J u l 1 5 N

  • v

1 5 J u l 1 6 A u g 1 6

HIV RNA [Kopien/ml] 200 400 600 800 1.000 1.200 1.400 1.600 1.800 2.000 CD4 [Zellen/µl]

67 9,8% <40 (n.d.) 22,5%

Therapieverlauf 44088

64

HIV RNA HCV RNA CD4 TDF FTC ETR DRV/r (bid) RAL DTG DRV/c TDF FTC

HCV Gt 4 Tranaminases ↑ Albumin → Thrombocyts → Fibroscan 6,6 kPa

TAF 12 weeks IFN+RBV stop due to non response & major depression

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SLIDE 25

HCV Gt 4 / Transaminases ↑ / Albumin → / Thrombocyts → Fibroscan 6,6 kPa HIV therapy: TAF/FTC, DRV/r (q.d.), DTG

Welche HCV Therapie? (2016/2017)

*(TDF)

  • Maviret (2017): Combination with DRV/r not recommended
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1 10 100 1.000 10.000 100.000 1.000.000 10.000.000

A u g 1 O k t 1 D e z 1 F e b 1 1 M a i 1 1 J u l 1 1 S e p 1 1 D e z 1 1 F e b 1 2 M r z 1 2 J u n 1 2 S e p 1 2 N

  • v

1 2 D e z 1 2 F e b 1 3 M a i 1 3 A u g 1 3 N

  • v

1 3 F e b 1 4 J u l 1 4 O k t 1 4 F e b 1 5 J u l 1 5 N

  • v

1 5 J u l 1 6 A u g 1 6 M r z 1 7 2 3 . 2 . 2 1 8

HIV RNA [Kopien/ml] 200 400 600 800 1.000 1.200 1.400 1.600 1.800 2.000 CD4 [Zellen/µl]

67 9,8% <40 (n.d.) 22,5%

Therapieverlauf 44088

64

HIV RNA HCV RNA CD4 TDF FTC ETR DRV/r (bid) RAL 12 weeks IFN+RBV stop due to non response & major depression DTG DRV/c TDF FTC TAF

LTFU from 03/2017 until 02/2018 !!!

313.000 cps/ml 119/µl (10,1%)

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SLIDE 27

RESISTENCE TEST 201816.02.18

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ULTRA DEEP SEQ 16.02.18 Restart ART, need for simplification, what to do?

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NEW ART … … AND FUTURE OPTION

13.03.2018 restarted ART (my decision): D/C/F/TAF 1 – 0 – 0 DTG 1 – 0 – 1 ! DRV 600 0 – 0 – 1 Cobi 150 0 – 0 – 1 Future Option: Simplification to

D/C/F/TAF + DTG qd (as soon as the VL is undetectable)

CHC treatment postponed until patient is stable again!

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30

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WHAT HAPPEND NEXT?

Week 2: HIV VL 1820 CD4 298µl (10,1%) Week 4 (30.04.2018): no show !!!!!!!!!!!!!! YESTERDAY he turned up – „missed a couple of doses…“

Future developement and lab are pending …

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Three cases:

  • One of those patients …(an update and new development)
  • It‘s never as as easy as one thinks!
  • Always ask twice!
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MSM, German, 49 years of age, HIV diagnosis 1994, CDC stage B2 (Herpes Zoster) First ART 2007 Co-Diagnoses:

Bronchial Asthma, Hypertension, Lactose intolerance

2011 first presentation at Praxis Hohenstaufenring

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HIV PCR undedetable since 11/2010 CD4 (01/2018) 669/µl (28,1%)

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SLIDE 36

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Resistance Test (incl. INI-gen)

WT !!!

Former Resistance Tests

WT (never actually failed on any of the past regimens!) Lab: No further abnormalities, no Syphilis, no Hepatitis On intensive questioning … almost interrogation! complete adherence, no missed doses no new medication no vitamins, minerals or antacids taken no substance abuse

any ideas ???

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SLIDE 37

ART switch: D/C/F/TAF

(agrees to this regimen, although he never wanted to taken a PI/r again – but tolerates it very well now) Ultra deep sequencing: WT down to a level of 10%! But finally we found a possible reason for the failing ART!

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SLIDE 38

21.03.2018 he complained of a (non STD) pharyngitis. Antibiosis: Amoxicillin 1000mg tdm Since he almost regularily suffers from diarrhea following any antibiotics he treated himself with lactobacilli TDM RAL was normal – BUT he had stopped Proflora 3 days prior to the lab-test…

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SLIDE 39

What‘s to do?

Stay on D/C/F/TAF? Back to F/TAF + RAL (patient is very keen on that…) Wait for NGS? Wait for B/F/TAF? Better to put him on F/TAF + DTG? … or could 3TC/DTG possibly suffice???

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? ?

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„The Temptation Of St. Antony“ by Ralph König

Thank you!